||| Original Article ||| DOI: 10.3329/bsmmuj.v10i4.34150

 

Plasma alpha-2-macroglobulin level in moderate to severe psoriasis

Md. Sahidullah Sikder, Mohammed Saiful Islam Bhuiyan, S. M. Manzurul Haque, Khondoker Anwarul Islam and Sheikh Md. Khorshed Alam

Department of Dermatology and Venereology, Faculty of Medicine, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh (MSS, MSIB); Department of Surgery, Sentara Care Plex Hospital, 3000 Coliseum Dr. Hammpton, VA 23666, Virginia, USA (SMMH); Bridge Division, Ministry of Bridge and Highway, Government of Bangladesh, Dhaka, Bangladesh (KAI); Department of Biochemistry and Molecular Biology, Faculty of Basic Science and Paraclinical Science, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh (SMKA)

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Abstract

Psoriasis is a T-cell mediated chronic inflammatory diseases where pro-inflammatory mediators are involved in its pathogenesis. Alpha-2-macroglobulin (α-2M) is a panproteinase inhibitor having unique clearing role of different cytokines. This study was conducted on 30 patients with moderate to severe psoriasis to see the plasma level of α-2M and was compared with the normal healthy controls. Patients who were already selected for systemic treatment (methotrexate) and consented for routine blood test for monitoring at baseline and 12 weeks after treatment were enrolled along with 10 healthy controls. The venous blood (5 mL) was collected and the plasma alfa-2 macroglobulin was estimated using the enzyme-linked immunosorbent assay. The mean plasma α-2M level was 3.0 ± 0.4 g/L among the normal healthy persons, and 2.8 ± 0.7 g/L among the untreated patients of psoriasis (p>0.05). Its level among the patients with psoriasis after systemic antipsoriatic drugs was 2.8 ± 0.6 g/L which was not significantly different from the baseline level (p>0.05). The study shows that the plasma α-2M level in psoriasis is not different comparing with normal healthy persons


Introduction

Psoriasis is a chronic inflammatory skin disease that affects 0.96 to 3% of different ethnic populations.1-3 Total burden of this chronic disabling disease; its physical, social and psychological load justifies continuous research on pathogenesis and management of psoriasis. Psoriasis is a T cell mediated disease, associated with aberrant inflammation and the production of pro-inflammatory mediators including TNF-α, IL-17, IL-23, and other cytokines (IL-1α, IL-1β, IL-6, IL-15, IL-18 and IL-20).4-7 Psoriasis is associated with a range of co-morbidities that include some chronic inflammatory conditions with overlapping pathology including rheumatoid arthritis, inflammatory bowel disease and other metabolic diseases.8

The α2 macroglobulin (α-2M) serving as a unique panproteinase inhibitor also involved in binding and the removal of cytokines support a balanced and properly functioning immune system in mammalian body.9-11 It is a carrier of various cytokines and growth factors (e.g. IL-6, IL-1β, transforming growth factor-β, basic fibroblast growth factor, nerve growth factor) and many of these have some regulating role over T and B cells12-13 So, the causal or beneficial role of this pan-proteinase in different inflammatory or autoimmune disease like psoriasis is needed to be explored which may open a new door in the treatment of these disease.

The current study was conducted to see the plasma concentration of alfa-2 macroglobulin among thirty patients with moderate to severe psoriasis who were already selected for treating with systemic treatment.


Materials and Methods

The study protocol was approved by the Institutional Review Board (IRB) of the University (BSMMU/2015/8200; Date 23/6/2015). The written consent was taken from each of the 30 patients of moderate to severe psoriasis who were already selected and consented for screening the blood test before systemic anti-psoriatic medication and 10 healthy adults.

The venous blood (5 mL) was collected and was sent to the Center for Advanced Biomedical Research of Bangabandhu Sheikh Mujib Medical University, where the plasma α-2M was estimated using the enzyme-linked immunosorbent assay (ELISA). Blood samples were also taken from all the patients with psoriasis after treatment with systemic drug as a part of their routine follow-up.

Data were analyzed for mean (M), median, Standard deviation, the mean error of the average (SEM) and variation coefficient (V%). Significance of differences between the averages was tested by the Student’s t-test.


Results

In the current study, 20 psoriasis patients were from the age group of 18 to 40 years. The mean age among the psoriatics were 35.8 with a range 15-67 years. Male to female ratio of psoriatic patients were 2:1 (Table I). The mean of plasma level of alfa-2 macroglobulin (α-2M) was 3.0 ± 0.4 among normal healthy persons (control group), and 2.8 ± 0.7 among untreated patients of psoriasis (p>0.05) (Table II). Its level among patients with psoriasis after systemic antipsoriatic drugs was 2.8 ± 0.6 which was not significantly different from baseline level (p>0.05).

Table I
Distribution of patients of psoriasis by demographic variables
ControlPatient
 (n = 10)(n = 30)
Mean age in year(range) 32.235.8
 (17-70)(15-67)
Age group  
<18 years11
18-40 years620
>40 years39
Sex (Male: Female)3:022:01

Table II
Distribution plasma alpha-2-macroglobulin level
ControlPatients of psoriasis  
 (n = 10)(n = 30) 
   Before treatmentAfter treatment
Alpha-2-macroglobulin (g/L)3.0 ± 0.42.8 ± 0.72.8 ± 0.6


Discussion

Complex interactions between T cells, dendritic cells, keratinocytes, neutrophils and the pro-inflammatory cytokines produced by these cells contribute to the initiation and perpetuation of cutaneous inflammation characteristic of psoriasis.14-15 A2M, a protease inhibitor having some clearing role on cytokines of tissue.9-15 We conducted the current study to see its serum level in psoriasis patients and compared with normal healthy controls. Globally only two previous studies have been conducted to see the alpha-2-macroglobulin activity in psoriasis.16-17

In both studies, the plasma A2M level is higher among people with psoriasis comparing with normal healthy controls and significantly got down after treatment with systemic medication.15-16 On the contrary, its level in the psoriasis patients were not different from that of Bangladeshi normal healthy individuals and even not changed after systemic medication.


Conclusion

As only few studies have been carried out to see the activity of A2M in psoriasis and our findings are not consistent with previous findings we propose further large studies on this issue.

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Acknowledgement

This study was funded by Bangabandhu Sheikh Mujib Medical University Research Grant and the biochemical analysis was done at the Center for Advanced Biomedical Research of BSMMU.


References

1. Gibbs S. Skin disease and socioeconomic conditions in rural Africa: Tanzania. Int J Dermatol. 1996; 35: 633–39.

2. Reich K, Krüger K, Mössner R, Augustin M. Epidemiology and clinical pattern of psoriatic arthritis in Germany: A prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis. Br J Dermatol. 2009; 160: 1040-47.

3. Danielsen K, Olsen AO, Wilsgaard T, Furberg AS. Is the prevalence of psoriasis increasing? A 30-year follow-up of a population-based cohort. Br J Dermatol. 2013; 168: 1303-10.

4. Bhuiyan MSI, Zakaria ASM, Sultana A, Haque AKM, Shawkat SM. Clinico-epidemiological study of childhood psoriasis. Bangabandhu Sheikh Mujib Med Univ J. 2017; 10: 119-22.

5. Rabin F, Bhuiyan SI, Islam T, Haque MA, Islam MA. Psychiatric and psychological comorbidities in patients with psoriasis: A review. Mymensingh Med J. 2012; 21: 780-86.

6. Liu J, Chen M, Wang X. Calcitonin generelated peptide inhibits lipopolysaccharide-induced interleukin-12 release from mouse peritoneal macrophages, mediated by the cAMP pathway. Immunology 2000; 101: 61-67.

7. Sheibanie AF, Tadmori I, Jing H, Vassiliou E, Ganea D. Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. FASEB J. 2004; 18: 1318-20.

8. Ritch K. The concept of psoriasis as a systemic inflammation: Implications for disease management. J Eur Academ Dermatol Venereol. 2012; 26 Suppl 2: 3-11.

9. Abe K, Yamamoto K, Sinohara H. Proteinase inhibitory spectrum of mouse murinoglobulin and α-macroglobulin. J Biochem. 1989; 106: 564-68.

10. Gonias SL, Pizzo SV. Conformation and protease binding activity of binary and ternary human alpha 2-macroglobulin-protease complexes. J Biol Chem. 1983; 258: 14682-85.

11. French K, Yerbury JJ, Wilson MR. Protease activation of alpha-2-macroglobulin modulates a chaperone-like action with broad specificity. Biochemistry 2008; 47: 1176–85.

12. Borth W. α-2 Macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J. 1992; 6: 3345–53.

13. LaMarre J, Wollenberg GK, Gonias SL, Hayes MA. Cytokine binding and clearance properties of proteinase-activated alpha-2-macroglobulins. Lab Invest. 1991; 65: 3–14.

14. Krueger JG. Hiding under the skin: A welcome surprise in psoriasis. Nat Med. 2012; 18: 1750-51.

15. Johnson-Huang LM, Lowes MA, Krueger JG. Putting together the psoriasis puzzle: An update on developing targeted therapies. Dis Model Mech. 2012; 5: 423-33.

16. Rocha-Peireira P, Santos-Silva A, Rebelo I, Figueiredo A, Quintanilhas A, Teixeira F. Clinical and laboratory investigations the inflammatory response in mild and in severe psoriasis. Br J Dermatol. 2004; 150: 917-28.

17. Chodorowska G, Wojnowska D, Juszkiewicz-Borowiec M. Creactive protein and α-2-macroglobulin plasma activity in medium-severe and severe psoriasis. JEADV. 2004; 1: 180-83.